Why does Covid-19 virus harm some more than others? 2 studies blame it on genetic defects, faulty immune system

As scientists try to flesh out the reasons behind it, a new theory has emerged that suggests a faulty early immune response to the new coronavirus is to be blamed


                            Why does Covid-19 virus harm some more than others? 2 studies blame it on genetic defects, faulty immune system
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Covid-19 does not affect people equally: some barely realize they are infected, others die within days. As scientists try to flesh out the reasons behind it, a new theory has emerged that suggests a faulty early immune response to the new coronavirus is to be blamed. This is according to two new studies.

The early immune response involves a group of proteins called interferons. When they detect a virus, they alert the immune system and activate other immune cells called killer T cells. These cells destroy infected cells in the body, thereby preventing further spread. But when interferons fail to act, individuals could become vulnerable. "We think timing may be essential because it’s only in the very early phase one can really battle the virus particles and defend against infection," Alexander Hoischen, head of the genomic technologies and immuno-genomics group at Radboud University Medical Center in Nijmegen, told Bloomberg.

"These findings provide compelling evidence that the disruption of type I interferon is often the cause of life-threatening Covid-19," Jean-Laurent Casanova, head of the St Giles Laboratory of Human Genetics of Infectious Diseases at The Rockefeller University and a Howard Hughes Medical Institute investigator, said in a statement. "And at least in theory, such interferon problems could be treated with existing medications and interventions."

But what keeps the interferons from acting against the Covid-19 virus in some patients? According to the two new studies, genetic defects or a dysfunctional immune system could be blamed. More than 10% of people with severe disease have misguided antibodies that attack the immune system, instead of the virus. And at least 3.5% carry a particular genetic mutation, according to the researchers.

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To arrive at these findings, Casanova and his colleagues looked at thousands of Covid-19 patients to study whether genetic defects had something to do with disease severity. First, they obtained blood samples from more than 650 patients with life-threatening coronavirus infection, 14% of whom had died. They compared these samples with another group of over 530 people who either had no symptoms or had mild disease.

They found that people with severe Covid-19 had defects or mutations in 13 genes. Further experiments showed that immune cells from these patients did not produce any detectable type I interferons in response to the new coronavirus.
 
Next, the team looked at the role of the immune system. Over 10% of the 987 patients with life-threatening Covid-19 had antibodies that attacked interferons. Of them, 94% were men, which could explain why this group is more vulnerable to Covid-19. "All of these findings strongly indicate that these auto-antibodies are actually the underlying reason some people get very sick and not the consequence of the infection," Casanova says.

On a positive note, some existing treatments offer hope. Casanova points out that two types of interferons are already available as drugs and are approved for use to treat certain conditions such as chronic viral hepatitis, an inflammation of the liver commonly caused by hepatitis B and C viruses. Further studies should test if they can help Covid-19 as well, he added. 

The two findings are published in Science.

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